The overall objective of this research project is to further our understanding of regulatory control mechanisms in the immune system by conducting a thorough analysis of certain aspects of the mechanisms of lymphocyte activation and cooperative cell interactions that occur in the development of most immune responses. These studies will make use of the model system involving cooperative responses between carrier-specific T lymphocytes and hapten-specific B lymphocytes in the development of immune responses to hapten-carrier conjugates utilizing a variety of experimental approaches both in vivo and in vitro. In vivo systems are designed to permit analysis of the mechanisms of T cell regulatory control involved in the stimulation of B lymphocytes of the IgE as well as IgG and IgM antibody classes. The conditions most conducive to development of enhancing and/or suppressive T cell influences on antibody production will be thoroughly analyzed. In the case of IgE antibody responses, recently discovered biologically-active molecules that appear to be produced in physiologic responses of intact animals, can be recovered from the serum of such animals, and which act selectively to either suppress or enhance IgE responses will be fully characterized. The studies in the IgE system will be ultimately aimed toward development of suitable methodology, based upon the information obtained in this program, for willfully manipulating levels of IgE antibody synthesis either downward or upward depending upon the need. We are also continuing our studies designed to determine the spectrum of regulatory control of immune responses that can be exerted by nonspecific means, such as the allogeneic effect, analysis of certain questions concerning control of immune responses by immune response or Ir genes and further attempts to elucidate, at the cellular and molecular level, mechanisms underlying certain types of immunological tolerance. Collectively, these studies should considerably widen our understanding of how immune regulation evolves and, under normal circumstances, maintains a steady state to foster maximum protection of the host.